ФАРМАКОГЕНЕТИЧНІ МАРКЕРИ ПРИ ТЕРАПІЇ ГОСТРОГО ЛІМФОБЛАСТНОГО ЛЕЙКОЗУ В ДІТЕЙ
DOI:
https://doi.org/10.15407/exp-oncology.2025.04.408Ключові слова:
гострий лімфобластний лейкоз, фармакогенетика, хіміотерапія, токсичність, дитяча онкологіяАнотація
Гострий лімфобластний лейкоз (ГЛЛ) є найпоширенішим злоякісним новоутворенням у дітей. Незважаючи на значний прогрес у терапії, лікування ГЛЛ залишається серйозним викликом. Терапевтичні протоколи базуються на використанні комбінацій хіміотерапевтичних препаратів. Хоча такі комбінації підвищують ефективність лікування, вони водночас ускладнюють оцінку токсичності. Варіабельність виникнення токсичних реакцій під час терапії ГЛЛ у дітей може бути зумовлена наявністю генетичних варіантів, які впливають як на фармакокінетику, так і на фармакодинаміку хіміотерапевтичних засобів. В огляді узагальнено та проаналізовано найзначущі й найкраще вивчені на сьогодні фармакогенетичні маркери, асоційовані з токсичністю та ефективністю хіміотерапевтичних препаратів, що застосовуються для лікування дитячого ГЛЛ. Розглянуто фармакогенетич- ні маркери для таких препаратів, як антрацикліни (доксорубіцин, даунорубіцин), вінкристин, кортикостероїди (преднізон, дексаметазон), L-аспарагіназа, метотрексат, алкілуючі агенти (циклофосфамід, іфосфамід), 6-меркаптопурин, цитарабін та етопозид. Наразі лише декілька генів — TPMT і NUDT15 — мають добре підтверджене клінічне значення, тоді як клінічна релевантність фармакогенетичних маркерів для інших препаратів, що застосовуються в терапії дитячого ГЛЛ, залишається предметом подальших досліджень. В огляді також окреслено основні прогалини в сучасних знаннях і визначено перспективні напрями подальших досліджень, спрямованих на впровадження фармакогенетичного тестування в клінічну практику. Таким чином, введення фармакогенетичного тестування в протоколи педіатричної онкології є важливим кроком до персоналізованого лікування ГЛЛ.
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